BreCaHAD: A dataset for breast cancer histopathological annotation and diagnosis

Objectives: Histopathological tissue analysis by a pathologist determines the diagnosis and prognosis of most tumors, such as breast cancer. To estimate the aggressiveness of cancer, a pathologist evaluates the microscopic appearance of a biopsied tissue sample based on morphological features which have been correlated with patient outcome. Data description: This paper introduces a dataset of 162 breast cancer histopathology images, namely the breast cancer histopathological annotation and diagnosis dataset (BreCaHAD) which allows researchers to optimize and evaluate the usefulness of their proposed methods. The dataset includes various malignant cases. The task associated with this dataset is to automatically classify histological structures in these hematoxylin and eosin (H&E) stained images into six classes, namely mitosis, apoptosis, tumor nuclei, non-tumor nuclei, tubule, and non-tubule. By providing this dataset to the biomedical imaging community, we hope to encourage researchers in computer vision, machine learning and medical fields to contribute and develop methods/tools for automatic detection and diagnosis of cancerous regions in breast cancer histology images. © 2019 The Author(s)

A Pan-Canadian Validation Study for the Detection of EGFR T790M Mutation Using Circulating Tumor DNA From Peripheral Blood

Introduction: Genotyping circulating tumor DNA (ctDNA) is a promising noninvasive clinical tool to identify the EGFR T790M resistance mutation in patients with advanced NSCLC with resistance to EGFR inhibitors. To facilitate standardization and clinical adoption of ctDNA testing across Canada, we developed a 2-phase multicenter study to standardize T790M mutation detection using plasma ctDNA testing. Methods: In phase 1, commercial reference standards were distributed to participating clinical laboratories, to use their existing platforms for mutation detection. Baseline performance characteristics were established using known and blinded engineered plasma samples spiked with predetermined concentrations of T790M, L858R, and exon 19 deletion variants. In phase II, peripheral blood collected from local patients with known EGFR activating mutations and progressing on treatment were assayed for the presence of EGFR variants and concordance with a clinically validated test at the reference laboratory. Results: All laboratories in phase 1 detected the variants at 0.5 % and 5.0 % allele frequencies, with no false positives. In phase 2, the concordance with the reference laboratory for detection of both the primary and resistance mutation was high, with next-generation sequencing and droplet digital polymerase chain reaction exhibiting the best overall concordance. Data also suggested that the ability to detect mutations at clinically relevant limits of detection is generally not platform-specific, but rather impacted by laboratory-specific practices. Conclusions: Discrepancies among sending laboratories using the same assay suggest that laboratory-specific practices may impact performance. In addition, a negative or inconclusive ctDNA test should be followed by tumor testing when possible

Representative transcript sets for evaluating a translational initiation sites predictor

<p>Abstract</p> <p>Background</p> <p>Translational initiation site (TIS) prediction is a very important and actively studied topic in bioinformatics. In order to complete a comparative analysis, it is desirable to have several benchmark data sets which can be used to test the effectiveness of different algorithms. An ideal benchmark data set should be reliable, representative and readily available. Preferably, proteins encoded by members of the data set should also be representative of the protein population actually expressed in cellular specimens.</p> <p>Results</p> <p>In this paper, we report a general algorithm for constructing a reliable sequence collection that only includes mRNA sequences whose corresponding protein products present an average profile of the general protein population of a given organism, with respect to three major structural parameters. Four representative transcript collections, each derived from a model organism, have been obtained following the algorithm we propose. Evaluation of these data sets shows that they are reasonable representations of the spectrum of proteins obtained from cellular proteomic studies. Six state-of-the-art predictors have been used to test the usefulness of the construction algorithm that we proposed. Comparative study which reports the predictors' performance on our data set as well as three other existing benchmark collections has demonstrated the actual merits of our data sets as benchmark testing collections.</p> <p>Conclusion</p> <p>The proposed data set construction algorithm has demonstrated its property of being a general and widely applicable scheme. Our comparison with published proteomic studies has shown that the expression of our data set of transcripts generates a polypeptide population that is representative of that obtained from evaluation of biological specimens. Our data set thus represents "real world" transcripts that will allow more accurate evaluation of algorithms dedicated to identification of TISs, as well as other translational regulatory motifs within mRNA sequences. The algorithm proposed by us aims at compiling a redundancy-free data set by removing redundant copies of homologous proteins. The existence of such data sets may be useful for conducting statistical analyses of protein sequence-structure relations. At the current stage, our approach's focus is to obtain an "average" protein data set for any particular organism without posing much selection bias. However, with the three major protein structural parameters deeply integrated into the scheme, it would be a trivial task to extend the current method for obtaining a more selective protein data set, which may facilitate the study of some particular protein structure.</p

Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray

Aberrations in the GI/S transition of the cell cycle have been observed in many malignancies and seem to be critical in the transformation process. Few studies have delineated the presence of GI/S regulatory defects and their clinical relevance in renal cell carcinoma (RCC). Therefore, we have examined the protein contents of cyclin D 1, D3, E, and p27 in 218 RCCs, using tissue microarray and immunohistochemistry. The results from a subset of tumours were confirmed by Western blotting and immunohistochemical staining of regular tissue sections. Interestingly, low protein contents of cyclin D I and p27 were associated with high nuclear grade, large tumour size, and poor prognosis for patients with conventional tumours. We further observed substantial differences in the pattern of GI/S regulatory defects between the different RCC subtypes. The majority of both conventional and papillary cases expressed p27; however, chromophobe tumours generally lacked p27 staining. In addition, conventional RCCs often expressed high cyclin DI protein levels, while papillary RCCs exhibited high cyclin E. In summary, we have shown that GI/S regulatory defects are present in RCC and are associated with clinico-pathological parameters. The pattern of cell cycle regulatory defects also differed between RCC subtypes. (C) 2003 Cancer Research UK

Cell cyclins: triggering elements of cancer or not?

Cyclins are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation. Recent studies have also revealed more mechanisms through which cyclins can express their oncogenic potential. This review focuses on the aberrant expression of G1/S cyclins and especially cyclin D and cyclin E; the pathways through which they lead to tumour formation and their involvement in different types of cancer. These elements indicate the mechanisms that could act as targets for cancer therapy

The idiotypic response to ferredoxin in mice

These investigations define a new protein idiotypic system-:- that of Clostridium pasteurianum ferredoxin (Fd). Previous studies from our laboratory have shown that the response to Fd, a small, non-mammalian electron transport protein is controlled by H-2K/I-A linked loci in mice and is almost a unideterminant response in H-2[sup k] mice. Strains of mice varying in Igh, Igl, and H-2 loci were immunized with Fd. Their Fd-immune sera were tested by inhibition in the ELISA with four specific anti-(anti-Fd)- idiotypes produced in rabbits to the purified, pooled anti-Fd sera from four different strains of mice. Major idiotypes were observed reproducibly in the anti-Fd responses of AKR/J, RF/J, and B10.BR/SnJ mice, while the anti-A/J idiotype did not reproducibly inhibit a high frequency of A/J anti-Fd antisera. Significant differences were observed between the levels of inhibition of pooled or individually analyzed anti-Fd antisera from the same mice. Further experiments showed that anti-Fd antisera from B10.BR mice have a high frequency of cross-reactivity with AKR/J anti-Fd idiotypes as do RF/J, C58/J, C3H/HeJ and CBA/J antisera. C58/J, C57BR/cdJ, and RF/J antisera also cross-react significantly with A/J anti-Fd idiotypes. Curiously, A/J and AKR/J anti-Fd antisera are not inhibited with anti-RF idiotype, and AKR anti-Fd antisera are not inhibited with anti-B10.BR idiotype. The idiotype profile of monoclonal anti-Fd antibodies was studied. The results demonstrated interstrain idiotypic cross-reactivity that paralled the results obtained with the serum antibodies of the appropriate mouse strain. These data, with the data from experiments utilizing serum antibodies do not demonstrate a correlation between idiotypic cross-reactivity and Igh or Igl allotypes. H-2 genes were observed to vary the pattern of idiotype expression in BIO recombinant mice, but no correlation between H-2 genes and idiotype expression could be observed. These results demonstrate that the anti-Fd response in H-2 mice is very complex with many intra and interstrain cross-reactive idiotypic families. Confirmatory results from 2-D electrophoretic analyses show-the presence- of many light chains in the anti-Fd response: These data are discussed in the context of existing hapten, carbohydrate, and protein antigenic systems, as well as in the context of current theories of idiotypic structure and antibody cross-reactivity.Science, Faculty ofMicrobiology and Immunology, Department ofGraduat

Molecular biology primer for the pediatric pathologist

Recent advances in the knowledge of molecular events of cell growth and differentiation have provided considerable gains to the understanding of neoplasia. Along with this understanding, molecular biology has yielded many new techniques of great potential for diagnostic use. This review illustrates, in general terms, current models of gene regulation, intracellular signal transduction, and the regulation of cell division that are relevant to pediatric pathologists. These concepts are used to examine the molecular pathology of three pediatric tumors: retinoblastoma, Wilms' tumor, and neuroblastoma. In addition, molecular biology techniques potentially useful to pediatric pathologists are discussed, with examples of some possible applications of these techniques. Hopefully, this review portrays the relevance of molecular biology to pediatric pathologists and serves as a useful guide to the interpretation of the molecular pathology literature

The Influence of GEAR UP on Academic Achievement and College Enrollment for Low SES Learners

The purpose of this quantitative correlation study was to examine the association between participation in the GEAR UP program with academic achievement and college enrollment for low SES students. The non-experimental design for this quantitative correlation study assessed associations between participation in the GEAR UP program, academic achievement, and college enrollment for low SES students in New Jersey. Archival data was retrieved from NCES and NCCEP on the GEAR UP program and analyzed for the results. The results showed that there is a significant relationship between participation in GEAR UP and college entrance for low SES students, and there is a significant relationship between participation in GEAR UP and academic achievement for low SES students

Chromosome mapping of human CDC25A and CDC25B phosphatases

The human CDC25 tyrosine phosphatases trigger activation of CDC2 by removing inhibitory phosphates; thus the genes encoding these phosphatases may be suspected as potential oncogenes due to their role in promoting cell division. To date, three human CDC25 genes have been identified: CDC25A, B, and C. This communication describes the mapping of CDC25A to chromosome 3p21 and CDC25B to chromosome 20p13 by fluorescence in situ hybridization with confirmation by the polymerase chain reaction of hamster-human somatic cell hybrid DNA. 3p21 is near an area frequently involved in karyotypic abnormalities in renal carcinomas, small cell carcinomas of the lung, and benign tumors of the salivary gland. 20p13 does not seem to be a common area for karyotypic alteration in tumors. Mapping of these genes to their chromosomal loci may help identify tumors with abnormal regulation of CDC25 genes due to genomic alterations

Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes

Cyclin dependent kinases (CDK's) are kinases that interact with cyclins and regulate cell division. Genomic clones encoding human CDK2, CDK4, and CDK5 were obtained and mapped to their respective chromosomal loci using fluorescence in situ hybridization on human lymphocyte metaphase spreads. Interestingly, CDK2 and CDK4 were located at the same position, 12q13, and CDK5 was mapped to 7q36. 12q13 has been shown to be associated with chromosome alterations such as amplifications and translocations in solid tumors. 7q36 does not appear to be a major site of chromosome alterations in tumors. As CDK2 and CDK4 appear to be important in regulating the human cell cycle, it is possible that the alterations of the 12q13 locus in tumors may involve changes in the regulation of CDK2 and CDK4 genes